engleski

Serotonin transporter polymorphism, platelet serotonin concentration and sleep disturbances in veterans with post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder, which develops after exposure to traumatic experience(s). Sleep disorders, such as nightmares and insomnia, are hallmarks of PTSD. Although the neurobiological basis of PTSD is not fully elucidated, this disorder most likely results from complex interactions between genetic and environmental factors. It has been suggested that serotonin (5- HT) system, due to its important role in controlling mood, arousal, and sleep, is involved in the development of PTSD symptoms. Several studies have investigated the association of functional polymorphism located in the 5-HT transporter gene (5-HT transporter linked polymorphic region, 5-HTTLPR) with sleep disturbances, however the findings are contradictory. The basic function of 5-HT transporter is re-uptake of 5-HT into presynaptic neuron or platelets, and 5-HTTLPR modulates the transcriptional activity of 5-HT transporter gene, influencing mRNA and protein levels. Since platelets and 5- HT neurons share similar biochemical processes, such as intake, storage, release and degradation of 5-HT, as well as the expression of 5-HT transporter and some 5-HT receptors, the concentration of platelet 5-HT may be used as a peripheral marker of certain PTSD symptoms. Therefore, the aim of this study was to determine the possible association of 5-HTTLPR and platelet 5-HT concentrations with sleep disorders in Croatian war veterans with PTSD. Croatian male, medication-free war veterans with PTSD (N=393), with or without comorbid depression and various sleep disturbances, were evaluated using the Structured Clinical Interview (SCID) based on DSM- IV criteria, the Hamilton Rating Scale for Anxiety (HAMA), the Hamilton Depression Scale (HDRS) and the Clinician Administered PTSD Scale (CAPS). Veterans with PTSD were subdivided according to sleep disturbances in those with or without insomnia and other sleep disturbances (nightmares, interrupted sleep). Genomic DNA was extracted from peripheral blood using a salting out method. Genotyping was performed using polymerase chain reaction (PCR) and DNA fragments were separated on a 2% agarose gel and visualized. 5-HT concentration was determined spectrofluorimetrically in platelets isolated from platelet rich plasma by series of centrifugations. All data were evaluated using GraphPad Prism version 4.00. Significantly higher frequency of the LL genotype of the 5- HTTLPR compared to S carriers and significantly higher platelet 5-HT concentrations were detected in veterans with PTSD with early insomnia compared to veterans with PTSD without early insomnia. Other sleep disturbances were not associated with 5-HTTLPR genotypes or platelet 5-HT concentration in veterans with PTSD with or without comorbid depression. Further studies with larger groups should clarify the association of 5-HTTLPR and platelet 5-HT with sleep disturbances in PTSD.

PTSD ; Sleep disturbances ; serotonin ; gene polymorphism ; transporter

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